Iatrogenic sciatic nerve injury in eighteen dogs and nine cats (1997-2006)

OBJECTIVE: To report clinical features associated with iatrogenic peripheral nerve injury in dogs and cats admitted (1997-2006) to a referral teaching hospital. STUDY DESIGN: Retrospective study. ANIMALS: Dogs (n=18), 9 cats. METHODS: Patients had acute signs of monoparesis attributable to sciatic nerve dysfunction that developed after treatment. Neurologic examination and electrodiagnostic testing were performed. Surgical therapy was used for nerve entrapment and delayed reconstructive surgery used in other cases. RESULTS: Of 27 nerve injuries, 25 resulted from surgery (18 with treatment of pelvic injuries). Iliosacral luxation repair resulted in tibial (4 cats) and peroneal (3 dogs) nerve dysfunction. Other causes were intramedullary pinning of femoral fractures (3), other orthopedic surgery (cemented hip prosthesis [2] and tibial plateau-leveling osteotomy [1]), and perineal herniorrhaphy [1]. Nerve injury occurred after intramuscular injection (1 cat, 1 dog). Immediate surgical treatment was removal of intramedullary nails, extruded cement, or entrapping suture. Delayed nerve transplantation was performed in 2 dogs. Within 1 year, 13 patients recovered completely, clinical improvement occurred in 7, and there was no improvement in 7. Five of the 7 dogs that did not recover had acetabular or ilium fracture. CONCLUSION: Iatrogenic sciatic nerve injury occurred most commonly during treatment of pelvic orthopedic diseases and had a poor prognosis. Clinical variation in sciatic nerve dysfunction in dogs and cats can be explained by species anatomic differences. CLINICAL RELEVANCE: Iatrogenic sciatic nerve injury leads to severely debilitating locomotor dysfunction with an uncertain prognosis for full-functional recovery.

Attenuation of myocardial reperfusion injury in pigs by Mirococept, a membrane-targeted complement inhibitor derived from human CR1

OBJECTIVES: Membrane-targeted application of complement inhibitors may ameliorate ischemia/reperfusion (I/R) injury by directly targeting damaged cells. We investigated whether Mirococept, a membrane-targeted, myristoylated peptidyl construct derived from complement receptor 1 (CR1) could attenuate I/R injury following acute myocardial infarction in pigs. METHODS: In a closed-chest pig model of acute myocardial infarction, Mirococept, the non-tailed derivative APT154, or vehicle was administered intracoronarily into the area at risk 5 min pre-reperfusion. Infarct size, cardiac function and inflammatory status were evaluated. RESULTS: Mirococept targeted damaged vasculature and myocardium, significantly decreasing infarct size compared to vehicle, whereas APT154 had no effect. Cardioprotection correlated with reduced serum troponin I and was paralleled by attenuated local myocardial complement deposition and tissue factor expression. Myocardial apoptosis (TUNEL-positivity) was also reduced with the use of Mirococept. Local modulation of the pro-inflammatory and pro-coagulant phenotype translated to improved left ventricular end-diastolic pressure, ejection fraction and regional wall motion post-reperfusion. CONCLUSIONS: Local modification of a pro-inflammatory and pro-coagulant environment after regional I/R injury by site-specific application of a membrane-targeted complement regulatory protein may offer novel possibilities and insights into potential treatment strategies of reperfusion-induced injury.

MRI-based brain volumetry in chronic whiplash patients: no evidence for traumatic brain injury

INTRODUCTION: Cognitive complaints, such as poor concentration and memory deficits, are frequent after whiplash injury and play an important role in disability. The origin of these complaints is discussed controversially. Some authors postulate brain lesions as a consequence of whiplash injuries. Potential diffuse axonal injury (DAI) with subsequent atrophy of the brain and ventricular expansion is of particular interest as focal brain lesions have not been documented so far in whiplash injury. OBJECTIVE: To investigate whether traumatic brain injury can be identified using a magnetic resonance (MR)-based quantitative analysis of normalized ventricle-brain ratios (VBR) in chronic whiplash patients with subjective cognitive impairment that cannot be objectively confirmed by neuropsychological testing. MATERIALS AND METHODS: MR examination was performed in 21 patients with whiplash injury and symptom persistence for 9 months on average and in 18 matched healthy controls. Conventional MR imaging (MRI) was used to assess the volumes of grey and white matter and of ventricles. The normalized VBR was calculated. RESULTS: The values of normalized VBR did not differ in whiplash patients when compared with that in healthy controls (F = 0.216, P = 0.645). CONCLUSIONS: This study does not support loss of brain tissue following whiplash injury as measured by VBR. On this basis, traumatic brain injury with subsequent DAI does not seem to be the underlying mechanism for persistent concentration and memory deficits that are subjectively reported but not objectively verifiable as neuropsychological deficits.

Non-invasive neurally adjusted ventilatory assist in rabbits with acute lung injury

OBJECTIVE: Neurally adjusted ventilatory assist uses the electrical activity of the diaphragm (EAdi)-a pneumatically-independent signal-to control the timing and pressure of the ventilation delivered, and should not be affected by leaks. The aim of this study was to evaluate whether NAVA can deliver assist in synchrony and proportionally to EAdi after extubation, with a leaky non-invasive interface. DESIGN AND SETTING: Prospective, controlled experimental study in an animal laboratory. ANIMALS: Ten rabbits, anesthetized, mechanically ventilated. INTERVENTIONS: Following lung injury, the following was performed in sequential order: (1) NAVA delivered via oral endotracheal tube with PEEP; (2) same as (1) without PEEP; (3) non-invasive NAVA at unchanged NAVA level and no PEEP via a single nasal prong; (4) no assist; (5) non-invasive NAVA at progressively increasing NAVA levels. MEASUREMENTS AND RESULTS: EAdi, esophageal pressure, blood gases and hemodynamics were measured during each condition. For the same NAVA level, the mean delivered pressure above PEEP increased from 3.9[Symbol: see text]+/-[Symbol: see text]1.4[Symbol: see text]cmH(2)O (intubated) to 7.5[Symbol: see text]+/-[Symbol: see text]3.8[Symbol: see text]cmH(2)O (non-invasive) (p[Symbol: see text]<[Symbol: see text]0.05) because of increased EAdi. No changes were observed in PaO(2) and PaCO(2). Increasing the NAVA level fourfold during non-invasive NAVA restored EAdi and esophageal pressure swings to pre-extubation levels. Triggering (106[Symbol: see text]+/-[Symbol: see text]20[Symbol: see text]ms) and cycling-off delays (40[Symbol: see text]+/-[Symbol: see text]21[Symbol: see text]ms) during intubation were minimal and not worsened by the leak (95[Symbol: see text]+/-[Symbol: see text]13[Symbol: see text]ms and 33[Symbol: see text]+/-[Symbol: see text]9[Symbol: see text]ms, respectively). CONCLUSION: NAVA can be effective in delivering non-invasive ventilation even when the interface with the patient is excessively leaky, and can unload the respiratory muscles while maintaining synchrony with the subject's demand.

Online correlation of spontaneous arterial and intracranial pressure fluctuations in patients with diffuse severe head injury

Determination of relevant clinical monitoring parameters for helping guide the intensive care therapy in patients with severe head injury, is one of the most demanding issues in neurotrauma research. New insights into cerebral autoregulation and metabolism have revealed that a rigid cerebral perfusion pressure (CPP) regimen might not be suitable for all severe head injured patients. We thus developed an online analysis technique to monitor the correlation (AI rho) between the spontaneous fluctuations of the mean arterial blood pressure (MABP) and the intracranial pressure (ICP). In addition, brain tissue oxygen (PtiO2) and metabolic microdialysate measures including glucose and lactate were registered. We found that in patients with good outcome, the AI rho values were significantly lower as compared with patients with poor outcome. Accordingly, microdialysate glucose and lactate were significantly higher in the good outcome group. We conclude that online determination of AI rho offers a valuable additional and technically easily performable tool for guidance of therapy in patients with severe head injury.

Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis

Bacteriolytic antibiotics cause the release of bacterial components that augment the host inflammatory response, which in turn contributes to the pathophysiology of brain injury in bacterial meningitis. In the present study, antibiotic therapy with nonbacteriolytic daptomycin was compared with that of bacteriolytic ceftriaxone in experimental pneumococcal meningitis, and the treatments were evaluated for their effects on inflammation and brain injury. Eleven-day-old rats were injected intracisternally with 1.3 x 10(4) +/- 0.5 x 10(4) CFU of Streptococcus pneumoniae serotype 3 and randomized to therapy with ceftriaxone (100 mg/kg of body weight subcutaneously [s.c.]; n = 55) or daptomycin (50 mg/kg s.c.; n = 56) starting at 18 h after infection. The cerebrospinal fluid (CSF) was assessed for bacterial counts, matrix metalloproteinase-9 levels, and tumor necrosis factor alpha levels at different time intervals after infection. Cortical brain damage was evaluated at 40 h after infection. Daptomycin cleared the bacteria more efficiently from the CSF than ceftriaxone within 2 h after the initiation of therapy (log(10) 3.6 +/- 1.0 and log(10) 6.3 +/- 1.4 CFU/ml, respectively; P < 0.02); reduced the inflammatory host reaction, as assessed by the matrix metalloproteinase-9 concentration in CSF 40 h after infection (P < 0.005); and prevented the development of cortical injury (cortical injury present in 0/30 and 7/28 animals, respectively; P < 0.004). Compared to ceftriaxone, daptomycin cleared the bacteria from the CSF more rapidly and caused less CSF inflammation. This combined effect provides an explanation for the observation that daptomycin prevented the development of cortical brain injury in experimental pneumococcal meningitis. Further research is needed to investigate whether nonbacteriolytic antibiotic therapy with daptomycin represents an advantageous alternative over current bacteriolytic antibiotic therapies for the treatment of pneumococcal meningitis.

Multiple pathways of neuroprotection against oxidative stress and excitotoxic injury in immature primary hippocampal neurons

In the immature brain hydrogen peroxide accumulates after excitotoxic hypoxia-ischemia and is neurotoxic. Immature hippocampal neurons were exposed to N-methyl-D-aspartate (NMDA), a glutamate agonist, and hydrogen peroxide (H(2)O(2)) and the effects of free radical scavenging and transition metal chelation on neurotoxicity were studied. alpha-Phenyl-N-tert.-butylnitrone (PBN), a known superoxide scavenger, attenuated both H(2)O(2) and NMDA mediated toxicity. Treatment with desferrioxamine (DFX), an iron chelator, at the time of exposure to H(2)O(2) was ineffective, but pretreatment was protective. DFX also protected against NMDA toxicity. TPEN, a metal chelator with higher affinities for a broad spectrum of transition metal ions, also protected against H(2)O(2) toxicity but was ineffective against NMDA induced toxicity. These data suggest that during exposure to free radical and glutamate agonists, the presence of iron and other free metal ions contribute to neuronal cell death. In the immature nervous system this neuronal injury can be attenuated by free radical scavengers and metal chelators.

Brain injury in experimental neonatal meningitis due to group B streptococci

We have characterized the pattern of brain injury in a rat model of meningitis caused by group B streptococci (GBS). Infant rats (12-14 days old; n = 69) were infected intracisternally with 10 microliters of GBS (log10(2.3) to 4.5 colony-forming units). Twenty hours later, illness was assessed clinically and cerebrospinal fluid was cultured. Animals were either immediately euthanized for brain histopathology or treated with antibiotics and examined later. Early GBS meningitis was characterized clinically by severe obtundation and seizures, and histopathologically by acute inflammation in the subarachnoid space and ventricles, a vasculopathy characterized by vascular engorgement, and neuronal injury that was most prominent in the cortex and often followed a vascular pattern. Incidence of seizures, vasculopathy and neuronal injury correlated with the inoculum size (p < 0.01). Early injury was almost completely prevented by treatment with dexamethasone. Within days after meningitis, injured areas became well demarcated and showed new cellular infiltrates. Thirty days post-infection, brain weights of infected animals treated with antibiotics were decreased compared to uninfected controls (1.39 +/- 0.18 vs 1.64 +/- 0.1 g; p < 0.05). Thus, GBS meningitis in this model caused extensive cortical neuronal injury resembling severe neonatal meningitis in humans.